Variant 2-203726685-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006139.4(CD28):c.105G>A(p.Ala35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,613,932 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 4 hom., cov: 32)

Exomes 𝑓: 0.012 ( 131 hom. )

Consequence

CD28
NM_006139.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.24

Variant links:

Genes affected

CD28 (HGNC:1653): (CD28 molecule) The protein encoded by this gene is essential for T-cell proliferation and survival, cytokine production, and T-helper type-2 development. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

CD28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-203726685-G-A is Benign according to our data. Variant chr2-203726685-G-A is described in ClinVar as [Benign]. Clinvar id is 774413.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CD28	NM_006139.4 linkuse as main transcript	c.105G>A	p.Ala35=	synonymous_variant	2/4	ENST00000324106.9
CD28	NM_001410981.1 linkuse as main transcript	c.147G>A	p.Ala49=	synonymous_variant	2/4
CD28	NM_001243077.2 linkuse as main transcript	c.105G>A	p.Ala35=	synonymous_variant	2/4
CD28	NM_001243078.2 linkuse as main transcript	c.53-2963G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD28	ENST00000324106.9 linkuse as main transcript	c.105G>A	p.Ala35=	synonymous_variant	2/4	1	NM_006139.4	P1	P10747-1
CD28	ENST00000458610.6 linkuse as main transcript	c.147G>A	p.Ala49=	synonymous_variant	2/4	1			P10747-7
CD28	ENST00000374481.7 linkuse as main transcript	c.53-2963G>A		intron_variant		1			P10747-2

Frequencies

GnomAD3 genomes

AF:

0.00740

AC:

1124

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00603

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00908

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00712

AC:

1791

AN:

251418

Hom.:

AF XY:

0.00701

AC XY:

952

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00799

GnomAD4 exome

AF:

0.0117

AC:

17136

AN:

1461830

Hom.:

131

Cov.:

AF XY:

0.0112

AC XY:

8175

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000510

Gnomad4 FIN exome

AF:

0.0102

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.00739

AC:

1124

AN:

152102

Hom.:

Cov.:

AF XY:

0.00751

AC XY:

558

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00239

Gnomad4 AMR

AF:

0.00602

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000625

Gnomad4 FIN

AF:

0.00908

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00996

Hom.:

Bravo

AF:

0.00722

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.00960

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.0

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over